Tamatinib free base
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MedKoo CAT#: 205926

CAS#: 841290-80-0 (free base)

Description: Tamatinib, also known as R406, is a potent inhibitor of immunoglobulin E (IgE)- and IgG-mediated activation of Fc receptor signaling (EC(50) for degranulation = 56-64 nM). The primary target for R406 is the spleen tyrosine kinase (Syk). R406 inhibited phosphorylation of Syk substrate linker for activation of T cells in mast cells and B-cell linker protein/SLP65 in B cells. R406 bound to the ATP binding pocket of Syk and inhibited its kinase activity as an ATP-competitive inhibitor (K(i) = 30 nM).


Chemical Structure

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Tamatinib free base
CAS# 841290-80-0 (free base)

Theoretical Analysis

MedKoo Cat#: 205926
Name: Tamatinib free base
CAS#: 841290-80-0 (free base)
Chemical Formula: C22H23FN6O5
Exact Mass: 470.1714
Molecular Weight: 470.45
Elemental Analysis: C, 56.17; H, 4.93; F, 4.04; N, 17.86; O, 17.00

Price and Availability

Size Price Availability Quantity
5.0mg USD 90.0 Ready to ship
10.0mg USD 150.0 Ready to ship
25.0mg USD 250.0 Ready to ship
50.0mg USD 450.0 Ready to ship
100.0mg USD 750.0 Ready to ship
200.0mg USD 1350.0 Ready to ship
500.0mg USD 2650.0 Ready to ship
1.0g USD 3850.0 Ready to ship
2.0g USD 6250.0 Ready to ship
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Related CAS #: 841290-81-1 (besylate)   841290-80-0 (free base)    

Synonym: R 406, R406, R406, Tamatinib

IUPAC/Chemical Name: 6-((5-fluoro-2-((3,4,5-trimethoxyphenyl)amino)pyrimidin-4-yl)amino)-2,2-dimethyl-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one

InChi Key: NHHQJBCNYHBUSI-UHFFFAOYSA-N

InChi Code: InChI=1S/C22H23FN6O5/c1-22(2)20(30)28-19-13(34-22)6-7-16(27-19)26-18-12(23)10-24-21(29-18)25-11-8-14(31-3)17(33-5)15(9-11)32-4/h6-10H,1-5H3,(H3,24,25,26,27,28,29,30)

SMILES Code: O=C1NC2=NC(NC3=NC(NC4=CC(OC)=C(OC)C(OC)=C4)=NC=C3F)=CC=C2OC1(C)C

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not soluble in water.

Shelf Life: >5 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Biological target: R406 free base inhibits Syk kinase activity in vitro with an IC50 of 41 nM, and also inhibits Lyn (IC50=63 nM) and Lck (IC50=37 nM).
In vitro activity: Among these, R406, an FDA-approved Syk inhibitor, was found to exhibit higher cytotoxicity in senescent HDFs than in non-senescent cells over the tested range of concentration (from 1 to 20 μM; Figure 1A). In addition, this study further confirmed R406-induced cytotoxicity by Hoechst 33342 staining, because CCK-1-based cell viability assay could reflect cell metabolic activity, which might be influenced by kinase inhibitors. Similar to the CCK-1 assay, the fluorescence levels of senescent HDFs were reduced by R406 in a dose dependent manner (Supplementary Figure 2C). These results demonstrated that R406 has cytotoxicity selectively in senescent fibroblasts in the RS model and, subsequent experiments were performed using R406 concentration of 10 μM. Reference: Aging (Albany NY). 2020 May 15; 12(9): 8221–8240. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7244031/
In vivo activity: LPS-induced increase in all of these inflammatory parameters was blocked by SYK inhibitor, R406 (Fig. 1A–E). Mice which underwent LPS-induced ALI had higher mortality rate at the end of 5-day period as compared to other groups, i.e. PBS group, SYKinhib group, and LPS + SYKinhib group (Fig. 1F). These findings show that SYK inhibition results in amelioration of LPS-induced ALI which is associated with reduced mortality. Reference: Int Immunopharmacol. 2019 Mar;68:39-47. https://pubmed.ncbi.nlm.nih.gov/30611000/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 13.17 27.99
DMF 0.5 1.06

Preparing Stock Solutions

The following data is based on the product molecular weight 470.45 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Cho HJ, Yang EJ, Park JT, Kim JR, Kim EC, Jung KJ, Park SC, Lee YS. Identification of SYK inhibitor, R406 as a novel senolytic agent. Aging (Albany NY). 2020 May 7;12(9):8221-8240. doi: 10.18632/aging.103135. Epub 2020 May 7. PMID: 32379705; PMCID: PMC7244031. 2. Sun S, Xue D, Chen Z, Ou-Yang Y, Zhang J, Mai J, Gu J, Lu W, Liu X, Liu W, Sheng L, Lu B, Lin Y, Xing F, Chen Z, Mou Y, Yan G, Zhu W, Sai K. R406 elicits anti-Warburg effect via Syk-dependent and -independent mechanisms to trigger apoptosis in glioma stem cells. Cell Death Dis. 2019 May 1;10(5):358. doi: 10.1038/s41419-019-1587-0. PMID: 31043589; PMCID: PMC6494878. 3. Wang W, Ren S, Lu Y, Chen X, Qu J, Ma X, Deng Q, Hu Z, Jin Y, Zhou Z, Ge W, Zhu Y, Yang N, Li Q, Pu J, Chen G, Ye C, Wang H, Zhao X, Liu Z, Zhu S. Inhibition of Syk promotes chemical reprogramming of fibroblasts via metabolic rewiring and H2 S production. EMBO J. 2021 Jun 1;40(11):e106771. doi: 10.15252/embj.2020106771. Epub 2021 Apr 28. PMID: 33909912; PMCID: PMC8167362. 4. Nadeem A, Ahmad SF, Al-Harbi NO, Al-Harbi MM, Ibrahim KE, Kundu S, Attia SM, Alanazi WA, AlSharari SD. Inhibition of spleen tyrosine kinase signaling protects against acute lung injury through blockade of NADPH oxidase and IL-17A in neutrophils and γδ T cells respectively in mice. Int Immunopharmacol. 2019 Mar;68:39-47. doi: 10.1016/j.intimp.2018.12.062. Epub 2019 Jan 2. PMID: 30611000.
In vitro protocol: 1. Cho HJ, Yang EJ, Park JT, Kim JR, Kim EC, Jung KJ, Park SC, Lee YS. Identification of SYK inhibitor, R406 as a novel senolytic agent. Aging (Albany NY). 2020 May 7;12(9):8221-8240. doi: 10.18632/aging.103135. Epub 2020 May 7. PMID: 32379705; PMCID: PMC7244031. 2. Sun S, Xue D, Chen Z, Ou-Yang Y, Zhang J, Mai J, Gu J, Lu W, Liu X, Liu W, Sheng L, Lu B, Lin Y, Xing F, Chen Z, Mou Y, Yan G, Zhu W, Sai K. R406 elicits anti-Warburg effect via Syk-dependent and -independent mechanisms to trigger apoptosis in glioma stem cells. Cell Death Dis. 2019 May 1;10(5):358. doi: 10.1038/s41419-019-1587-0. PMID: 31043589; PMCID: PMC6494878.
In vivo protocol: 1. Wang W, Ren S, Lu Y, Chen X, Qu J, Ma X, Deng Q, Hu Z, Jin Y, Zhou Z, Ge W, Zhu Y, Yang N, Li Q, Pu J, Chen G, Ye C, Wang H, Zhao X, Liu Z, Zhu S. Inhibition of Syk promotes chemical reprogramming of fibroblasts via metabolic rewiring and H2 S production. EMBO J. 2021 Jun 1;40(11):e106771. doi: 10.15252/embj.2020106771. Epub 2021 Apr 28. PMID: 33909912; PMCID: PMC8167362. 2. Nadeem A, Ahmad SF, Al-Harbi NO, Al-Harbi MM, Ibrahim KE, Kundu S, Attia SM, Alanazi WA, AlSharari SD. Inhibition of spleen tyrosine kinase signaling protects against acute lung injury through blockade of NADPH oxidase and IL-17A in neutrophils and γδ T cells respectively in mice. Int Immunopharmacol. 2019 Mar;68:39-47. doi: 10.1016/j.intimp.2018.12.062. Epub 2019 Jan 2. PMID: 30611000.

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1: Lhermusier T, van Rottem J, Garcia C, Xuereb JM, Ragab A, Martin V, Gratacap MP, Sié P, Payrastre B. The Syk-kinase inhibitor R406 impairs platelet activation and monocyte tissue factor expression triggered by heparin-PF4 complex directed antibodies. J Thromb Haemost. 2011 Oct;9(10):2067-76. doi: 10.1111/j.1538-7836.2011.04470.x. PubMed PMID: 21848694.

2: Sweeny DJ, Li W, Grossbard E, Lau DT. Contribution of gut bacteria to the metabolism of the spleen tyrosine kinase (Syk) inhibitor R406 in cynomolgus monkey. Xenobiotica. 2010 Jun;40(6):415-23. doi: 10.3109/00498251003734244. PubMed PMID: 20415544.

3: Sweeny DJ, Li W, Clough J, Bhamidipati S, Singh R, Park G, Baluom M, Grossbard E, Lau DT. Metabolism of fostamatinib, the oral methylene phosphate prodrug of the spleen tyrosine kinase inhibitor R406 in humans: contribution of hepatic and gut bacterial processes to the overall biotransformation. Drug Metab Dispos. 2010 Jul;38(7):1166-76. doi: 10.1124/dmd.110.032151. Epub 2010 Apr 6. PubMed PMID: 20371637.

4: Quiroga MP, Balakrishnan K, Kurtova AV, Sivina M, Keating MJ, Wierda WG, Gandhi V, Burger JA. B-cell antigen receptor signaling enhances chronic lymphocytic leukemia cell migration and survival: specific targeting with a novel spleen tyrosine kinase inhibitor, R406. Blood. 2009 Jul 30;114(5):1029-37. doi: 10.1182/blood-2009-03-212837. Epub 2009 Jun 2. PubMed PMID: 19491390.

5: Spalton JC, Mori J, Pollitt AY, Hughes CE, Eble JA, Watson SP. The novel Syk inhibitor R406 reveals mechanistic differences in the initiation of GPVI and CLEC-2 signaling in platelets. J Thromb Haemost. 2009 Jul;7(7):1192-9. doi: 10.1111/j.1538-7836.2009.03451.x. Epub 2009 Apr 24. PubMed PMID: 19422460.

6: Zhu Y, Herlaar E, Masuda ES, Burleson GR, Nelson AJ, Grossbard EB, Clemens GR. Immunotoxicity assessment for the novel Spleen tyrosine kinase inhibitor R406. Toxicol Appl Pharmacol. 2007 Jun 15;221(3):268-77. Epub 2007 Mar 31. PubMed PMID: 17490694.

7: Braselmann S, Taylor V, Zhao H, Wang S, Sylvain C, Baluom M, Qu K, Herlaar E, Lau A, Young C, Wong BR, Lovell S, Sun T, Park G, Argade A, Jurcevic S, Pine P, Singh R, Grossbard EB, Payan DG, Masuda ES. R406, an orally available spleen tyrosine kinase inhibitor blocks fc receptor signaling and reduces immune complex-mediated inflammation. J Pharmacol Exp Ther. 2006 Dec;319(3):998-1008. Epub 2006 Aug 31. PubMed PMID: 16946104.